scholarly journals Disease stage‐specific G protein‐coupled receptor expression in clinical disorders: Chronic lymphocytic leukemia as a model

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Trishna Katakia ◽  
Fiona Murray ◽  
Lingzhi Zhang ◽  
Charles Gray ◽  
Paul Insel
2012 ◽  
Vol 53 (4) ◽  
pp. 665-673 ◽  
Author(s):  
Adriana C. Drost ◽  
Gabriele Seitz ◽  
Andreas Boehmler ◽  
Mirjam Funk ◽  
Karoline Pia Norz ◽  
...  

Cell ◽  
2008 ◽  
Vol 135 (3) ◽  
pp. 561-571 ◽  
Author(s):  
Jean B. Regard ◽  
Isaac T. Sato ◽  
Shaun R. Coughlin

Author(s):  
Ann M. Winter-Vann ◽  
Lynell Martinez ◽  
Cynthia Bartus ◽  
Agata Levay ◽  
George J. Turner

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4996-4996
Author(s):  
Gabriele Seitz ◽  
Sedat Yildirim ◽  
Andreas M. Boehmler ◽  
Lothar Kanz ◽  
Robert Möhle

Abstract Egress of lymphocytes from lymphoid organs into the circulation has been shown to depend on the presence of the lipid mediator sphingosine 1-phosphate (S1P) in the peripheral blood, and expression of corresponding S1P receptors (i.e., S1P1), that belong to the family of 7-transmembrane G protein-coupled receptors (GPCR). As circulating lymphocytic lymphoma cells are a hallmark of chronic lymphocytic leukemia, we analyzed expression of different S1P receptors and the effects of S1P on B-CLL cells. By qualitative and quantitative (TaqMan) RT-PCR, significant mRNA expression of S1P1 and S1P4 was found in CLL cell lines (EHEB, MEC-1) and in most samples (S1P1 in 88%, S1P4 in 100%) of primary CD19+ cells isolated from the peripheral blood of untreated B-CLL patients. mRNA of other S1P receptors (S1P2, S1P3, S1P5) was less consistently detected. Normal, nonmalignant B cells were strongly positive for S1P1, while other S1P receptors were weakly expressed or negative. S1P induced typical effects of chemotactic GPCR, such as actin polymerization (analyzed by flow cytometry) and chemotaxis (measured in a modified Boyden chamber assay) in CLL cell lines and primary B-CLL cells. After serum deprivation in vitro, S1P induced phosphorylation of ERK/MAP-kinase as analyzed by Western blot, demonstrating that S1P receptors expressed in CLL were able to activate signaling pathways of GPCR not only related to cell migration and chemotaxis, but also to cell proliferation. Of note, the S1P1 ligand FTY720, which induces receptor internalization after prolonged exposure and acts as an antagonist, resulted in apoptosis in CLL cell lines and primary CLL cells in vitro, as measured by MTT-test and staining with Annexin-FITC, respectively. We conclude that sphingosine 1-phosphate, which is present in the peripheral blood in considerable amounts, contributes to the trafficking of B-CLL cells expressing the GPCRs S1P1/4, and to their prolonged survival.


2009 ◽  
Vol 284 (49) ◽  
pp. 34103-34115 ◽  
Author(s):  
Yoon Namkung ◽  
Concetta Dipace ◽  
Eneko Urizar ◽  
Jonathan A. Javitch ◽  
David R. Sibley

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